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Table 2 Confirmed IEM by WES. n = 14

From: Whole exome sequencing diagnosis of inborn errors of metabolism and other disorders in United Arab Emirates

Gene (Isoform) Variants (PMID) Diagnosis (MIM) Comments
Mitochondrial inheritance
tRNA Ala m.5591G > Ab (16476954) MTTA (590000) Failure to thrive, ptosis, myopathy, normal mitochondrial studies on muscle biopsy.
ND5 m.13513G > A (p.D393N)b (12509858) MTND5 (516005) Developmental regression, dysmorphic features, esotropia, chorioretinal atrophy, seizure, left ventricular hypertrophy, renal insufficiency, brain image suggestive of Leigh syndrome.
X-Linked inheritance
PDHA1 (NM_000284) c.787C > G (p.R263G) (1508605) PDHAD (312170) Brain image suggestive of Leigh syndrome; low complex II (succinate dehydrogenase) activity in the fibroblasts. Two heterozygous (‘cis’ configuration) novel missense variants, c.321C > G (p.1107 M) and c.338A > T (p.N113I), in SDHA were found in patient and father.
Autosomal recessive inheritance
FBXL4 (NM_012160) c.1067delG (p.G356fs) (23993194) MTDPS13 (615471) Developmental regression, hypotonia, failure to thrive, microcephaly, lactic acidosis, normal fibroblast mitochondrial studies. Three siblings died in infancy.
C10orf2 (NM_021830) c.1198C > T (p.R400C) (21364701) MTDPS7 (271245) Developmental regression, hearing loss, scoliosis, reduced activities of complexes I & IV in myocytes; normal activities in fibroblasts. Two cousins with Leigh disease.
MTHFR (NM_005957) c.1596C > G(p.Y532) (a) MTHFRD (236250) Progressive encephalopathy, seizure, cerebral venous thrombosis, gangrenous like bullous formation in the leg, congenital heart disease, ↑homocysteine, ↓methionine.
PYCR2 (NM_013328) c.28C > T(p.Q10X) (a) HLD10 (616420) Developmental regression, failure to thrive, seizure, microcephaly, severe demyelination, thin corpus callosum.
c.796C > T(p.R266X) (a) Developmental delay, hypotonia, failure to thrive, microcephaly, thin corpus callosum, delayed myelination.
HEXA (NM_000520) c.2 T > C Tay-Sachs (268800) Developmental regression, failure to thrive, seizure disorders, dystonia, feeding difficulties constipation. Diagnosis confirmed by enzyme analysis.
HEXB (NM_000521) c.826_829del (p.E276fs) Sandhoff (268800) Developmental regression, failure to thrive, feeding difficulties, seizure, and vision loss.
SUMF1 (NM_182760) c.691dupT (p.W231fs) c.689A > G (p.E230ZG) MSD (272200) Developmental delay, seizure, hepatomegaly, delayed myelination, ↑urine sulfatide, ↑urine heparan sulphate.
UROC1 (NM_144639) c.855G > A (p.W285X) (a) UROCD (276880) Intellectual disabilities, attention deficit and hyperactivity disorder, hyperextensible joints, ↑imidazole propionate.
TBX19 (NM_005149) c.604-1G > C (a) IAD (201400) Intellectual disabilities, congenital hypothyroidism, two sisters died in infancy with hypoglycemia.
HSD3B7 (NM_025193) c.45_46del (p.G17fs) (12679481) CBAS1 (607765) Neonatal cholestasis, hepatosplenomegaly, hypotonia, failure to thrive.
  1. (a) Novel mutation; (b) heteroplasmic mutations (56-59 %). Mutations in bold are de novo, All mutations are homozygous, except those in Italics, which are heterozygous. PMID PubMed Identifier, MIM Mendelian Inheritance in Man, MTTA transfer RNA, mitochondrial, alanine, MTND5 complex I, subunit ND5, PDHAD pyruvate dehydrogenase e1-alpha deficiency, SDHA succinate dehydrogenase complex, subunit A, flavoprotein, MTDPS13 mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), MTDPS7 mitochondrial DNA depletion syndrome 7 (hepatocerebral type); MTHFRD methylenetetrahydrofolate reductase deficiency, HLD10 leukodystrophy, hypomyelinating 10, MSD multiple sulfatase deficiency, UROCD urocanase deficiency, IAD ACTH deficiency, CBAS1 bile acid synthesis defect, congenital, 1